The mutagenicities of sodium bisulfite and glutathione, reported earlier, appear to be mediated through the formation of oxygen- containing free radicals. The mutagenicity of bisulfite is inversely related to its rate of autooxidation in the medium, leading to the speculation that for mutagenesis to occur, unoxidized bisulfite must be present in sufficient quantities to enter the cell prior to its oxidation. Glutathione metabolism, followed by autooxidation of the resulting dipeptide, cysteinylglycine, leads to the extracellular formation of hydrogen peroxide which is a mutagen. Glutathione (and cysteinylglycine) mutagenicity is enhanced by substances or conditions that enhance the rate of oxidation and the formation of hydrogen peroxide, and is depressed by inhibitors of cysteinylglycine oxidation and hydrogen peroxide formation and accumulation. The mutagenic responses of two other sulfhydryl compounds, cysteine and penicillamine, appear to occur via a similar mechanism as cysteinylglycine, except that the oxidation reactions take place intracellularly.